(a) Field of the Invention
This invention relates to N-{2-, 3- and 4-[R.sub.1 (phenyl)-C(.dbd.X)]-phenyl-lower-alkyl} amines useful as anti-inflammatory agents.
(b) Description of the Prior Art
A very large class of organic compounds of widely diverse structural types are known to be useful as anti-inflammatory agents, but many of such anti-inflammatory agents are acidic, for example, .alpha.-(3-benzoylphenyl)propionic acid, known generically as ketoprofen (British Pat. No. 1,164,585, published Sept. 17, 1969). Such acidic agents are often irritating, and in some cases are ulcerogenic, to the gastric mucosa when administered orally. There is thus a great need for anti-inflammatory agents, for example compounds having a basic amine function, which might be expected to be non-irritating to the gastric mucosa. Although the chemical literature describes numerous types of amine-substituted compounds asserted to have anti-inflammatory activity [see for example U.S. Pat. Nos. 3,770,748, patented Nov. 6, 1973 and 3,803,127, patented Apr. 9, 1974 (N-phenylpolymethyleneimines); U.S. Pat. Nos. 3,772,311, patented Nov. 13, 1973 and 3,773,772, patented Nov. 20, 1973 (polymethyleneimino-lower-alkanoylpyrazoles); U.S. Pat. No. 3,773,944, patented Nov. 20, 1973 (1-[3-aminopropyl]phthalans); U.S. Pat. No. 3,801,594, patented Apr. 2, 1974 (3-amino-lower-alkylindoles); U.S. Pat. No. 3,810,985, patented May 14, 1974 (4-anilino-1,3,5-triazines) and French Patent No. 1,549,342, delivre Nov. 4, 1968 (4-[benzoylphenylmethyl]morpholines)], no such basic compounds are known to be commercially available, and none are known to be under advanced investigation by pharmacologists for possible commercial development. The search for an effective, non-acidic anti-inflammatory agent for commercial development has therefore continued.
My U.S. Pat. No. 4,069,256, which is identified above in the section headed RELATED APPLICATIONS, and several foreign patent publications corresponding thereto, for example Belgian Patent No. 837,706, granted July 20, 1976, disclose compounds having the formula I below where R.sub.1, R.sub.2, R.sub.3, &gt;C.dbd.X and N.dbd.B have each of the meanings given below with respect to the compounds of formula I except that, in the patent disclosures, the group R.sub.8 is defined as being only lower-alkyl or cyclohexyl, and the group corresponding to R.sub.9, in addition to the meanings given below with respect to the compounds of formula I, is defined as hydrogen.